Guerrini-Rousseau Léa, Varlet Pascale, Colas Chrystelle, Andreiuolo Felipe, Bourdeaut Franck, Dahan Karin, Devalck Christine, Faure-Conter Cécile, Genuardi Maurizio, Goldberg Yael, Kuhlen Michaela, Moalla Salma, Opocher Enrico, Perez-Alonso Vanessa, Sehested Astrid, Slavc Irene, Unger Sheila, Wimmer Katharina, Grill Jacques, Brugières Laurence
Department of Pediatric and Adolescents Oncology, Gustave Roussy Cancer Center, Paris-Saclay University, Villejuif, France.
Gustave Roussy Cancer Center, Unite Mixte de Recherche 8203, Centre National de la Recherche Scientifique, Paris-Saclay University, Villejuif, France.
Neurooncol Adv. 2019 Dec 2;1(1):vdz033. doi: 10.1093/noajnl/vdz033. eCollection 2019 May-Dec.
Malignant brain tumors (BT) are among the cancers most frequently associated with constitutional mismatch repair deficiency (CMMRD), a rare childhood cancer predisposition syndrome resulting from biallelic germline mutations in mismatch repair genes. This study analyzed data from the European "Care for CMMRD" (C4CMMRD) database to describe their clinical characteristics, treatments, and outcome with the aim of improving its diagnosis/treatment.
Retrospective analysis of data on patients with CMMRD and malignant BT from the C4CMMRD database up to July 2017.
Among the 87 registered patients, 49 developed 56 malignant BTs: 50 high-grade gliomas (HGG) (with giant multinucleated cells in 16/21 histologically reviewed tumors) and 6 embryonal tumors. The median age at first BT was 9.2 years [1.1-40.6], with nine patients older than 18. Twenty-seven patients developed multiple malignancies (including16 before the BT). Most patients received standard treatment, and eight patients immunotherapy for relapsed HGG. The 3- and 5-year overall survival (OS) rates were 30% (95% CI: 19-45) and 22% (95% CI: 12-37) after the first BT, with worse prognosis for HGG (3-year OS = 20.5%). Six patients were alive (median follow-up 2.5 years) and 43 dead (38 deaths, 88%, were BT-related). Other CMMRD-specific features were café-au-lait macules (40/41), multiple BTs (5/15), developmental brain anomalies (11/15), and consanguinity (20/38 families).
Several characteristics could help suspecting CMMRD in pediatric malignant BTs: giant cells on histology, previous malignancies, parental consanguinity, café-au-lait macules, multiple BTs, and developmental brain anomalies. The prognosis of CMMRD-associated BT treated with standard therapies is poor requiring new therapeutic up-front approaches.
恶性脑肿瘤（BT）是最常与遗传性错配修复缺陷（CMMRD）相关的癌症之一，CMMRD是一种罕见的儿童癌症易感综合征，由错配修复基因的双等位基因种系突变引起。本研究分析了欧洲“关爱CMMRD”（C4CMMRD）数据库的数据，以描述其临床特征、治疗方法和预后，旨在改善其诊断/治疗。
回顾性分析截至2017年7月C4CMMRD数据库中CMMRD和恶性BT患者的数据。
在87名登记患者中，49名发生了56例恶性BT：50例高级别胶质瘤（HGG）（在21例经组织学检查的肿瘤中有16例有巨大多核细胞）和6例胚胎性肿瘤。首次发生BT的中位年龄为9.2岁[1.1 - 40.6]，9名患者年龄超过18岁。27名患者发生了多种恶性肿瘤（包括16例在BT之前）。大多数患者接受了标准治疗，8例复发HGG患者接受了免疫治疗。首次BT后3年和5年总生存率（OS）分别为30%（95%CI：19 - 45）和22%（95%CI：12 - 37），HGG预后更差（3年OS = 20.5%）。6例患者存活（中位随访2.5年），43例死亡（38例死亡，88%与BT相关）。其他CMMRD特异性特征包括牛奶咖啡斑（40/41）、多发BT（5/15）、发育性脑异常（11/15）和近亲结婚（20/38个家庭）。
几个特征有助于怀疑儿童恶性BT中的CMMRD：组织学上的巨细胞、既往恶性肿瘤、父母近亲结婚、牛奶咖啡斑、多发BT和发育性脑异常。采用标准疗法治疗的CMMRD相关BT预后较差，需要新的前期治疗方法。
